regulating Archives - World Asthma Foundation

Natural products and their derivatives regulating the janus kinase/signal transducer and activator of transcription pathway.

J Asian Nat Prod Res. 2014 Jul;16(7):800-12

Authors: Lin Y, Wang F, Zhang GL

Abstract
Janus kinase/signal transducer and activator of transcriptions (JAK/STAT) signaling pathway is one of the major signaling pathways involved in a variety of human physiological and pathological process. The proteins of JAK/STAT pathway or interferon response element (such as JAK, STAT, Src, SOCS, 2’5′-OAS, and ISRE) might be as drug targets for the study of physiological processes and treatment of related diseases, including cell proliferation, differentiation, apoptosis and immune processes, inflammation, cancer, arthritis, asthma, diabetes, and other diseases. This review attempts to summarize the current status of natural products and their derivatives (2002-2013) regulating the proteins or transcription elements of JAK/STAT signaling pathway to supply a new direction or drug targets for the discovery of new drugs.

PMID: 25076196 [PubMed – in process]

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Mfge8 suppresses airway hyperresponsiveness in asthma by regulating smooth muscle contraction.

Proc Natl Acad Sci U S A. 2012 Dec 26;

Authors: Kudo M, Khalifeh Soltani SM, Sakuma SA, McKleroy W, Lee TH, Woodruff PG, Lee JW, Huang K, Chen C, Arjomandi M, Huang X, Atabai K

Abstract
Airway obstruction is a hallmark of allergic asthma and is caused primarily by airway smooth muscle (ASM) hypercontractility. Airway inflammation leads to the release of cytokines that enhance ASM contraction by increasing ras homolog gene family, member A (RhoA) activity. The protective mechanisms that prevent or attenuate the increase in RhoA activity have not been well studied. Here, we report that mice lacking the gene that encodes the protein Milk Fat Globule-EGF factor 8 (Mfge8(-/-)) develop exaggerated airway hyperresponsiveness in experimental models of asthma. Mfge8(-/-) ASM had enhanced contraction after treatment with IL-13, IL-17A, or TNF-?. Recombinant Mfge8 reduced contraction in murine and human ASM treated with IL-13. Mfge8 inhibited IL-13-induced NF-?B activation and induction of RhoA. Mfge8 also inhibited rapid activation of RhoA, an effect that was eliminated by an inactivating point mutation in the RGD integrin-binding site in recombinant Mfge8. Human subjects with asthma had decreased Mfge8 expression in airway biopsies compared with healthy controls. These data indicate that Mfge8 binding to integrin receptors on ASM opposes the effect of allergic inflammation on RhoA activity and identify a pathway for specific inhibition of ASM hypercontractility in asthma.

PMID: 23269839 [PubMed – as supplied by publisher]

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